Cardioprotective effect of diazepam on ischemia-reperfused isolated hyperthyroid rat heart
Hyperthyroidism increases the vulnerability of the heart to ischemia-reperfusion (I/R) injury. Regarding the fact that diazepam also affects cardiac I/R injury, the current study was conducted to investigate the effect of diazepam on ischemia-reperfused isolated hyperthyroid rat heart. The animals were divided into 6 groups: the control, hyperthyroid, control diazepam (1 mg/kg), hyperthyroid diazepam (1 mg/kg), control diazepam (5 mg/kg), and hyperthyroid diazepam (5 mg/kg) groups. Langendorff-perfused rat hearts underwent 40 min of global ischemia and 45 min of reperfusion. Different cardiac parameters, including the left ventricular developed pressure, heart rate, coronary flow, and rate pressure product (RPP), were measured. Lactate dehydrogenase (LDH) release was determined in reperfusion to evaluate the severity of the myocardial injury. The results showed that the RPP recovery percentage significantly decreased in the hyperthyroid group compared with control group, whereas comparison of the hyperthyroid diazepam (1 mg/kg) with the control and control diazepam (1 mg/kg) groups did not reveal a significant difference. These results were confirmed by LDH test, demonstrating that administration of diazepam (1 mg/kg) protected the heart against I/R injury in the hyperthyroid group and significantly decreased the I/R injury, which was probably due to the function of diazepam as a phosphodiesterase 4 inhibitor.
Cardioprotective effect of diazepam on ischemia-reperfused isolated hyperthyroid rat heart
Hyperthyroidism increases the vulnerability of the heart to ischemia-reperfusion (I/R) injury. Regarding the fact that diazepam also affects cardiac I/R injury, the current study was conducted to investigate the effect of diazepam on ischemia-reperfused isolated hyperthyroid rat heart. The animals were divided into 6 groups: the control, hyperthyroid, control diazepam (1 mg/kg), hyperthyroid diazepam (1 mg/kg), control diazepam (5 mg/kg), and hyperthyroid diazepam (5 mg/kg) groups. Langendorff-perfused rat hearts underwent 40 min of global ischemia and 45 min of reperfusion. Different cardiac parameters, including the left ventricular developed pressure, heart rate, coronary flow, and rate pressure product (RPP), were measured. Lactate dehydrogenase (LDH) release was determined in reperfusion to evaluate the severity of the myocardial injury. The results showed that the RPP recovery percentage significantly decreased in the hyperthyroid group compared with control group, whereas comparison of the hyperthyroid diazepam (1 mg/kg) with the control and control diazepam (1 mg/kg) groups did not reveal a significant difference. These results were confirmed by LDH test, demonstrating that administration of diazepam (1 mg/kg) protected the heart against I/R injury in the hyperthyroid group and significantly decreased the I/R injury, which was probably due to the function of diazepam as a phosphodiesterase 4 inhibitor.
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- Leducq-Alet N, Vin V, Savi P et al. TNF-alpha induced PMN apoptosis in whole human blood: protective eff ect of SSR180575, a potent and selective peripheral benzodiazepine ligand. Biochem Biophys Res Commun 399: 475-479, 2010. 6. Castedo M, Perfettini JL, Kroemer G. Mitochondrial apoptosis and the peripheral benzodiazepine receptor: a novel target for viral and pharmacological manipulation. J Exp Med 196: 1121- 1125, 2002.
- Li J, Wang J, Zeng Y. Peripheral benzodiazepine receptor ligand, PK11195 induces mitochondria cytochrome c release and dissipation of mitochondria potential via induction of mitochondria permeability transition. Eur J Pharmacol 560: 117-122, 2007.
- Leducq N, Bono F, Sulpice T et al. Role of peripheral benzodiazepine receptors in mitochondrial, cellular, and cardiac damage induced by oxidative stress and ischemia- reperfusion. J Pharmacol Exp Th er 306: 828-837, 2003.
- Bono F, Lamarche I, Prabonnaud V et al. Peripheral benzodiazepine receptor agonists exhibit potent antiapoptotic activities. Biochem Biophys Res Commun 265: 457-461, 1999.
- Carayon P, Portier M, Dussossoy D et al. Involvement of peripheral benzodiazepine receptors in the protection of hematopoietic cells against oxygen radical damage. Blood 87: 3170-3178, 1996.
- Shackebaei D, Kayhani B, Godini A et al. Th e eff ect of repeated diazepam administration on myocardial function in the ischemia-reperfused isolated rat heart. Saudi Med J 30: 755- 759, 2009.
- Calvo DJ, Medina JH. Regulation of peripheral-type benzodiazepine receptors following repeated benzodiazepine administration. Funct Neurol 7: 227-230, 1992.
- Kwak HJ, Park KM, Choi HE et al. PDE4 inhibitor, rofl umilast protects cardiomyocytes against NO-induced apoptosis via activation of PKA and Epac dual pathways. Cell Signal 20: 803- 814, 2008.
- Neethling WML, Hodge AJ. Th e eff ect of diazepam on myocardial function and coronary vascular tone aft er endotoxemia in the isolated rat heart model. Infl amm Res 59: 907-913, 2010.
- Juan-Fita MJ, Vargas ML, Hernández J. Diazepam enhances inotropic responses to dopamine in rat ventricular myocardium. Anesth Analg 102: 676-681, 2006.
- Ashida K, Katsura T, Saito H et al. Decreased activity and expression of intestinal oligopeptide transporter PEPT1 in rats with hyperthyroidism in vivo. Pharm Res 21: 969-975, 2004.
- Oztay F, Ergin B, Ustunova S et al. Eff ects of coenzyme Q10 on the heart ultrastructure and nitric oxide synthase during hyperthyroidism. Chin J Physiol 50: 217-224, 2007.
- Bell RM, Mocanu MM, Yellon DM. Retrograde heart perfusion: the Langendorff technique of isolated heart perfusion. J Mol Cell Cardiol 50: 940-950, 2011.
- Skrzypiec-Spring M, Grotthus B, Szelag A et al. Isolated heart perfusion according to Langendorff - still viable in the new millennium. J Pharmacol Toxicol Methods 55: 113-126, 2007.
- Masullo P, Venditti P, Agnisola C et al. Role of nitric oxide in the reperfusion induced injury in hyperthyroid rat hearts. Free Radic Res 32: 411-421, 2000.
- Venditti P, Masullo P, Agnisola C et al. Eff ect of vitamin E on the response to ischemia-reperfusion of Langendorff heart preparations from hyperthyroid rats. Life Sci 66: 697-708, 2000.
- Salvetti F, Chelli B, Gesi M et al. Eff ect of noise exposure on rat cardiac peripheral benzodiazepine receptors. Life Sci 66: 1165- 1175, 2000.
- Obame FN, Zini R, Souktani R et al. Peripheral benzodiazepine receptor-induced myocardial protection is mediated by inhibition of mitochondrial membrane permeabilization. J Pharmacol Exp Th er 323: 336-345, 2007.